Emerging Medications in Facial Nerve Recovery: A Systematic Review and Meta‐Analysis

Abstract

Objective

To systematically review the literature for medical therapies that promote facial nerve regeneration and recovery.

Data Sources

PubMed/Medline, Embase, and SCOPUS databases were searched for English‐language studies published from inception through May 2025.

Review Methods

Human studies evaluating the efficacy of medical therapy on facial nerve regeneration using validated facial nerve grading scales were included.

Results

Nine studies were included in qualitative analysis, and 6 were included in a meta‐analysis. Treatments included nimodipine (n = 6), pentoxifylline (n = 1), co‐enzyme Q10 (n = 1), and extracellular vesicles (n = 1). All studies used HB score, and recovery was defined as HB score ≤3. Recovery was observed in 94% (95% CI:[90%, 97%]) of patients treated with nimodipine and 84% (95% CI: [70%, 97%]) of control patients; this was not statistically significant (OR 2.26, 95% CI: [0.97, 5.26]). Nimodipine significantly decreased HB score by 1.66 (95% CI: [0.81, 2.52]) before and after treatment. Pentoxifylline and extracellular vesicles demonstrated some efficacy, while co‐enzyme Q10 was not efficacious.

Conclusion

Nimodipine improved HB score but was not significantly associated with recovery to HB score ≤3 compared to controls. Pentoxifylline and extracellular vesicles may have some efficacy, but co‐enzyme Q10 is not effective. Further research is required to uncover additional treatments.

Facial paralysis can arise from various etiologies, such as idiopathic, infectious, traumatic, neoplastic, and iatrogenic causes. Idiopathic facial palsy (Bell's palsy) is the most common diagnosis, affecting approximately 10 to 50 per 100,000 individuals. ¹ , ² One of the primary contributing pathogenetic mechanisms in idiopathic facial paralysis is inflammation and edema of the facial nerve; therefore, steroids are a key management option. ² Iatrogenic facial nerve injury most commonly occurs during parotid or vestibular schwannoma procedures. ³ While intraoperative neuromonitoring has decreased the number of iatrogenic injuries, injury to the facial nerve may sometimes be unpredictable or unavoidable due to the nature of the surgery.4, 5, 6

Facial paralysis has devastating effects on functional and psychosocial quality of life, hindering communication, eating, social interactions, and negatively affecting mental health. ⁷ , ⁸ While approximately 70% of patients with idiopathic facial paralysis demonstrate recovery within 6 months, a significant proportion do not reach full recovery. Recovery is multifactorial and can be less predictable depending on the extent and location of the injury. Depending on the etiology, treatment of facial paralysis may include watchful waiting, medical therapy, facial neuromuscular retraining (specialized facial therapy), and surgery. ² , ⁹ In the acute setting, facial nerve decompression may be used for specific indications to relieve compression and inflammation, while delayed surgical options attempt to restore resting symmetry and re‐establish motion. ²

Medical therapy offers a non‐invasive opportunity to promote facial nerve regeneration. Aside from steroids with or without antivirals for treatment of idiopathic facial paralysis, there is no consensus on other medications that facilitate nerve regeneration with the exception of targeted antibiotics for infectious etiologies. The purpose of this study is to systematically review the literature on emerging medications that promote facial nerve recovery and compare the efficacy of these treatments.

Method

Search Criteria

This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. ¹⁰ To identify studies for inclusion in this review, detailed search strategies were developed for the following 3 databases: PubMed (US National Library of Medicine, National Institutes of Health), Scopus (Elsevier), and EMBASE (Elsevier). Databases were searched from the date of inception through May 2025. Search terms were created based on a literature review on peripheral nerve regeneration. ¹¹ The search strategies used a combination of subject headings (eg, MeSH in PubMed) and keywords for the following concepts: “facial nerve paralysis,” “Bell's palsy,” “regeneration,” “treatment,” “medication,” “calcium channel blocker,” “steroid,” “antiviral,” “ozone,” “tacrolimus,” “bumetanide,” “melatonin,” “vitamin B12,” “growth hormone,” “ginkgo biloba,” “coenzyme Q,” and “carnitine.” The PubMed search strategy was modified for the other 2 databases, replacing MeSH terms with appropriate subject headings, when available, and maintaining similar keywords. To identify additional articles, the reference lists of relevant articles were hand‐searched. References were exported into the review management software, Covidence (Veritas Health Innovation Ltd.), for study selection.

Selection Criteria

Studies assessing the effect of medical therapy on facial paralysis were included. Studies were considered for inclusion if they were: (1) double‐ or single‐blinded randomized controlled trials, (2) double‐ or single‐blinded randomized comparison trials, (3) nonrandomized controlled trials, and (4) prospective or retrospective observational studies. Studies were excluded if they were literature reviews, systematic reviews, meta‐analyses, nonhuman studies, non‐English studies, included surgery or procedures as treatment, or lacked quantifiable data. Steroids and antivirals were part of the original key terms search to capture any drug given in addition to steroids or antivirals. Articles that evaluated only steroids and/or antivirals were excluded. There were no restrictions on country, race, gender, or date of publication. Abstracts were first independently assessed by at least 2 reviewers (KC, CM, BS, AU) with discrepancies resolved by a third reviewer (KC and CM).

Included articles were critically appraised to assess the level of evidence using the Oxford Center for Evidence‐Based Medicine criteria. ¹² Two authors (CM and KC) performed independent risk assessments. The risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions version 6.5. ¹³ The Risk of Bias in Non‐Randomized Studies—of Interventions (ROBINS‐I) tool was used specifically to evaluate non‐randomized studies. ¹⁴ The Risk of Bias 2 tool (RoB 2) was used specifically to evaluate randomized controlled trials. ¹⁵ Risk of bias for non‐randomized studies was graded as either low, moderate, serious, or critical for each aspect, and risk of bias for randomized studies was graded as either low or high.

Data Extraction

Data extraction was performed by 2 reviewers (KC and BS) independently. Data extracted from studies included year of publication, type of study, number of patients, patient demographics, medication used, dose and frequency of medication, follow‐up period, and outcomes. The studies graded the severity of facial paralysis using validated scales, including the House‐Brackmann (HB) scale, Sunnybrook scale, and Facial Grading System.

Statistical Analysis

Meta‐analysis of single proportions for different treatment groups was performed with Open Meta‐Analyst (Brown University, 2015). Meta‐analysis of continuous measures (comparison of means and standard deviations) between pretreatment and posttreatment groups was performed with Cochrane Review Manager (RevMan) version 5.4 (The Cochrane Collaboration, 2020). The random‐effects model was used, which assumes the true effects of studies are highly variable between different studies and provides the summary effect as a weighted average of the effects reported in the included studies. ¹⁶ The random‐effects model provides a more conservative estimate (ie, with a wider confidence interval [CI]), but better accounts for heterogeneity between various studies. Heterogeneity is evaluated with the I ² statistic, ranging from 0% to 100%. A P < 0.05 was considered to indicate a statistically significant difference.

Results

Qualitative Analysis

A total of 8327 articles were identified. After removing 1338 duplicate articles, 6987 articles underwent title and abstract screening. Of these, 175 articles were eligible for full‐text review, and 9 articles were ultimately included for data extraction (Figure 1). From the systematic review, there were additional drugs used in human and animal studies that were not included in the analysis due to data heterogeneity and a lack of validated facial paralysis grading scales.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) flow diagram reflecting independent searches of the PubMed/MEDLINE, Embase, and Scopus databases.

A total of 539 patients were included, and etiologies of facial paralysis included iatrogenic injury (n = 402) and idiopathic (n = 137) (Table 1). Treatments included nimodipine (n = 6), pentoxifylline (n = 1), co‐enzyme Q10 (n = 1), and extracellular vesicles ((ExoFlo™; n = 1). All studies used House‐Brackmann scores to assess facial nerve function. For most studies, success was defined as an improvement of the House‐Brackmann score ≤3.

Table 1.

Included Studies

Study, year	Study design	N	Male (n)	Mean Age (years)	Etiology	Facial grading	Medication	Timing of Tx		Dose & route	Duration	Follow‐up
Scheller, 2004	Retrospective	7	NR	50	Iatrogenic	HB	Nimodipine	R	10 days	15‐30 μg/kg/h IV	10 days	6 months
Scheller, 2012	Prospective	13	7	38	Iatrogenic	HB	Nimodipine	R	0 to 10 days	60 mg PO, 6 times/day	6 weeks	6‐8 weeks
Strauss, 2006	Retrospective	45	NR	Tx: 52 Control: 56	Iatrogenic	HB	Nimodipine	NR	NR	15‐30 μg/kg/h IV	10 days	12 months
Scheller, 2007	RCT	30	NR	Tx: 51 Control: 49	Iatrogenic	HB	Nimodipine	P	1 day before surgery	15‐30 μg/kg/h IV	8 days	2 years
Kunert, 2016	Retrospective	212	NR	46	Iatrogenic	HB	Nimodipine	P	3 days before surgery	60 mg PO, every 6 hrs	10 days	>6 months
Scheller, 2016	RCT	95	41	48	Iatrogenic	HB	Nimodipine	P	1 day before surgery	1‐2 mg/h IV	7 days	12 months
Shamanna, 2023	RCT	70	38	NR	Idiopathic	HB	Pentoxifylline	NR	NR	400 mg PO, TID	1 week	6 months
Ali, 2018	Prospective	60	28	35	Idiopathic	HB	Coenzyme Q10	R	Within 72 hr of onset	100 mg PO, daily	1 month	1 month
Dreschnack, 2023	Prospective	7	2	50	Idiopathic, iatrogenic	HB	ExoFlo	R	1‐10 years	13 cc IV, 2 cc tissue	Weeks 1, 2, 4	2 months

Abbreviations: HB, House‐Brackmann score; IV, intravenous; NR, not reported; P, prophylactic; PO, oral; POD, postoperative day; R, reactive; RCT, randomized controlled trial; TID, 3 times/day; Tx, treatment/intervention.

The treatment group in Shamanna et al had pentoxifylline in addition to the standard regimen, which consisted of prednisolone, acyclovir, pantoprazole with domperidone, hydroxymethyl cellulose eye drops, and facial physiotherapy. ¹⁷ The pentoxifylline group showed a significant difference in full recovery to HB 1 in 42.86% of patients with idiopathic facial palsy compared to 28.57% in the control group (P = .038, Table 2). ¹⁷ Ali et al showed that coenzyme Q10 plus prednisolone had a greater percentage of patients with HB improvement (90%) compared to prednisolone alone (76.7%) in patients with idiopathic facial palsy. However, this study did not define the degree of HB improvement, and no statistical significance was reported (P = .149, Table 2). ¹⁸ In a case series study, ExoFlo™ (extracellular vesicles) showed a mean improvement of HB score of 1.4 in patients with iatrogenic facial palsy or Bell's palsy who failed previous therapies.

Table 2.

Summary of Human Studies Other on Medications Than Nimodipine

Study, Year	Study design	N	Medication	Outcomes	P‐value
Shamanna, 2023	RCT	70	Pentoxifylline	HB improvement to 1 (full recovery):	.038
				Treatment group: 42.86% Control group: 28.57%
Ali, 2018	Prospective	60	Coenzyme Q10	HB improvement:	.149
				Treatment group: 90% (HB 2.23 ± 0.85) Control group: 77% (HB 2.13 ± 1.11)
Dreschnack, 2023	Prospective	7	Extracellular vesicles	Mean HB improvement: 1.4	N/A

Abbreviation: HB, House‐Brackman score.

Human Studies Not Meeting Inclusion Criteria

In humans, other drugs that have been studied include acetyl‐carnitine, methylcobalamin, and rhizoma pharmacupunture.19, 20, 21 These studies did not meet inclusion criteria due to the lack of standardized facial grading systems used to evaluate facial nerve function or was considered procedural. Acetyl‐carnitine and methylcobalamin demonstrated shorter recovery times compared to controls. ¹⁹ , ²⁰ Rhizoma pharmacupuncture showed statistically significant improvement in HB scores after 2 weeks compared to the control group. ²¹

Animal Studies

In animal models, drugs other than nimodipine that have been studied include: insulin‐like growth factor, tacrolimus, thymoquinone, melatonin, collagen‐binding NT‐3, valproic acid, testosterone, lipoprostaglandin, cortexin, lipoic acid, riluzole, polyethylene glycol, aminoguanine, agmatine sulphate, vitamin D, bromonidine, erythropoietin/darbepoetin, pyrrolopyrimidine, ginkgo biloba, ozone, etanercept, chitosan, memantine, and acetyl‐cysteine.22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 Medications that showed improvement in functional recovery (eg, whisking movement, vibrissae orientation, blink reflex, and/or eye closure) were nimodipine, darbepoetin, erythropoietin, memantine, etanercept, tacrolimus and platelet‐rich fibrin, ginkgo biloba, IGF‐1, n‐acetyl‐cysteine, and vitamin D.32, 38, 40, 42, 44, 46, 48, 54, 55, 56 On the microscopic level, nimodipine administration in rats demonstrated decreased inflammation, improved Schwann cell remyelination, accelerated axonal sprouting, reduced polyneuronal innervation of target muscles, and increased surviving motor neurons.57, 58, 59 Coenzyme Q10, lipoic acid, and ozone showed lower nerve stimulation thresholds in rats. ⁴¹ , ⁵³ , ⁶⁰ Medications that promoted axon regeneration and/or myelination (eg, number of axons, axon density, axon diameter, myelin thickness, reduced myelin debris) included bumetanide, agmatine sulphate, collagen‐binding NT3, thymoquinone, tacrolimus, ozone, aminoguanidine, melatonin, IGF‐1, methylcobalamin, and riluzole. ²⁴ , ²⁷ , ²⁸ , ³⁰ , ³¹ , ³³ , ⁴¹ , ⁴⁵ , ⁶¹ , ⁶² Pyrrolopyrimidine and valproic acid demonstrated improved neuronal survival, while brimonidine showed decreased neuroinflammation. ³⁵ , ³⁷ , ⁵⁹

Meta‐Analysis

Six studies were included in the meta‐analysis, all of which evaluated iatrogenic facial nerve injury and used nimodipine as the intervention (Table 1).63, 64, 65, 66, 67, 68 Follow‐up ranged from 6 to 8 weeks to 2 years. Successful recovery was observed in 94% (95% CI: [90%, 97%]) of patients treated with nimodipine (Figure 2A). In the control patients who were not treated with nimodipine, successful recovery was observed in 84% (95% CI:[70%, 97%]) of patients (Figure 2B). Differences in posttreatment HB scores between patients treated with nimodipine and controls were not statistically significant (OR 2.26, 95% CI: [0.97, 5.26]) (Figure 2C). Nimodipine significantly decreased HB scores by a mean difference of 1.66 (95% CI: [0.81, 2.52]) points (Figure 3).

Figure 2.

Meta‐analysis of single proportions of patients treated with nimodipine (A) controls (B) with successful recovery defined as House‐Brackmann score ≤3. Meta‐analysis of ratio measures of successful recovery in nimodipine versus controls (C).

Figure 3.

Meta‐analysis of mean difference of House‐Brackmann scores pre‐treatment compared to posttreatment.

Publication Bias

Publication bias was assessed with a funnel plot shown in Figure 4. A summary of the risk of bias is shown in Figure 5. Two of the 6 studies were considered to have serious risk of bias, while the other 4 studies had low or moderate risk of bias.

Figure 4.

Funnel plot for meta‐analysis of ratio measures for nimodipine.

Figure 5.

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.

Discussion

There are emerging medications that are being considered for facial nerve recovery, however, no consensus exists. Our systematic review shows that the most studied oral medication in humans for facial nerve recovery was nimodipine. Our meta‐analysis on nimodipine demonstrated that nimodipine improves HB scores when comparing pretreatment and posttreatment scores (mean difference 1.66, 95% CI: [0.81, 2.52], Figure 3). However, nimodipine did not significantly improve successful recovery (HB ≤3) when compared to controls (OR 2.26, 95% CI: [0.97, 5.26]). Coenzyme Q10 showed clinical improvement in HB scores but was not statistically significant when compared to controls. Pentoxifylline was used in 1 study, and it showed statistical significance in improving HB scores compared to the control group. ¹⁷ A small case series using ExoFlo™ in patients who failed previous therapies demonstrated improvement in HB scores in all patients, but no statistical analysis was performed. In animal models, there were additional medications that were investigated that showed improvement in functional recovery, axon regeneration, myelination, and lower nerve stimulation thresholds. However, it is unclear whether the benefits seen in animal models can be translated into clinical improvement in humans.

Nerve recovery and regeneration are slow processes that involve proper blood supply and neurotrophic factors. ⁶⁹ Nerve injury can lead to excessive calcium influx into neuronal cells, which can disrupt the regulated release of neurotransmitters, leading to excitotoxicity and potentially apoptosis. ⁷⁰ Nimodipine is an L‐type calcium channel antagonist that is approved to treat hypertension and prevent vasospasms in the setting of subarachnoid hemorrhage. ⁷¹ , ⁷² It is thought that nimodipine has a neuroprotective effect due to its ability to reduce intracellular calcium overload. ⁵⁹ , ⁷⁰ In animal models with facial nerve injury, studies showed that nimodipine can help with axonal regrowth, remyelination, and recovery of whisking movement in rats.55, 57, 58, 59, 73 Chorath et al reported that nimodipine did not improve long‐term facial nerve function (OR 4.54, 95% CI: [0.25, 82.42]) but did improve hearing function (OR 2.78, 95% CI: [1.74, 4.45]). ⁷⁴ Compared to Chorath et al, our meta‐analysis included one additional study (Scheller 2016); however, our results similarly did not show a significant difference in successful recovery for nimodipine (Figure 2C). Conversely, another systematic review and meta‐analysis by Lin et al found an improvement in facial (OR 2.78; 95% CI: 1.20, 6.44) and vocal cord motion (OR 13.73; 95% [CI]: 6.21, 30.38) recovery with nimodipine in patients who underwent vestibular schwannoma surgery. ⁷⁵ For studies that did not have available data from the control groups, Lin et al used historical data from studies with similar patient populations, which could have affected the results. ⁷⁵ Nimodipine has been shown to improve laryngeal electromyography in recurrent laryngeal nerve injury, lending to believe similar results could occur with facial nerve injury.

The presence of a rich vascular supply has been shown to encourage nerve regeneration. ⁷⁶ Pentoxifylline is a phosphodiesterase inhibitor approved to treat claudication as a vasodilator. ⁷⁷ Some sources report that pentoxifylline also has anti‐inflammatory properties by affecting the TNF‐alpha pathway.77, 78, 79 It is hypothesized that pentoxifylline acts as a vasoactive agent to improve perfusion and delivery of nutrients needed for nerve and tissue recovery. ¹⁷ , ⁸⁰ Pentoxifylline has shown efficacy in neuroprotection in diabetic neuropathy and in improving axon regeneration; however, data on its neuroprotective role in facial nerve recovery are limited. ¹⁷ , ⁷⁹ , ⁸⁰ Shamanna et al demonstrated that vascular compromise may play a role in idiopathic facial palsy and the addition of a vasoactive agent may improve facial nerve recovery. Although the pentoxifylline group showed a difference in achieving full recovery to HB 1, both the treatment and control groups had 100% of patients recover to HB ≤3. While pentoxifylline showed some efficacy in improving recovery compared to standard treatment, no definitive conclusions can be drawn from the small sample size and limited data.

Oxidative stress may also play a role in idiopathic facial paralysis. ⁸¹ Antioxidants, such as coenzyme Q10 (ubiquinone), may help reduce oxidative stress and promote nerve recovery. Coenzyme Q10 is a lipid‐soluble enzyme cofactor in the mitochondrial electron transport chain that is found in every cell in the body with a membrane. ⁸² In neurodegenerative diseases, such as amyotrophic lateral sclerosis and Parkinson's disease, coenzyme Q10 has shown some protective benefits against neuronal loss. ⁸³ Ali et al found that adding coenzyme Q10 to standard steroid regimen in patients with idiopathic facial palsy shows improvement in HB scores. ¹⁸ Although the results were not statistically significant, coenzyme Q10 could still have a meaningful clinical significance. ¹⁸

ExoFlo™ is a drug that contains extracellular vesicles, which are lipid membrane‐bound particles containing protein, RNA, and other bioactive materials. ⁸⁴ Extracellular vesicles have shown promise in axonal regrowth, vascular regeneration, and inflammatory regulation, all of which support a desirable environment for nerve regeneration. ⁸⁵ , ⁸⁶ Dreschnack et al performed a pilot study using ExoFlo™ in 7 patients with facial paralysis despite previous treatments, 4 of whom had idiopathic and 3 had iatrogenic causes. ⁸⁷ ExoFlo™ was administered intravenously and injected into the soft tissue surrounding the facial nerve. Although the sample size from this study was small, ExoFlo™ demonstrated an improvement in House‐Brackmann scores in all 7 patients with persistent facial paralysis. ExoFlo™ may show promise in promoting facial nerve regeneration; however, larger studies and long‐term data are needed to determine the efficacy and safety of this new drug.

Limitations

Limitations to this study include the retrospective nature of a systematic review, lack of control groups, heterogeneity of studies, and a small number of human studies on medications that promote recovery of facial nerve palsy. The facial nerve grading scale used in the studies included in this systematic review was the HB scale. Although the HB scale has utility and practicality, it is limited in grading more nuanced facial nerve recovery. More specific grading scales, such as the Sunnybrook Facial Grading System, would provide more detail on facial nerve recovery. Additionally, recovery was defined as HB score ≤3, which does not represent normal facial function or functional recovery in some cases. Patients with a HB score of 3 may still require intervention or reanimation surgery; thus HB score ≤3 may not be a good indicator of clinical or functional recovery. There were additional human studies using methylcobalamin and acetyl‐carnitine, but the outcomes in the studies did not use validated facial nerve grading scales and were excluded from this study. Due to the retrospective nature of systematic reviews, we were unable to re‐validate data or control for missing/heterogeneous data. Some studies lacked control groups, making it difficult to truly compare the effectiveness of the treatment. The timing of the intervention in each of the studies varied, ranging from prophylactic intervention to years after facial paralysis onset. The heterogeneity in the timing of treatment (prophylactic vs. reactive), duration of treatment (8 days to 6 weeks), and variability in follow‐up (6‐8 weeks to 2 years) make it difficult to truly assess the efficacy of nimodipine in the acute phase of facial nerve paralysis. Additionally, Kunert et al had the biggest sample size and, therefore, had the greatest influence on the meta‐analysis for nimodipine. ⁶⁷ We recognize that the variability in the studies is a major limitation and makes it difficult to provide clinical guidance based on the results of this systematic review. Since facial nerve recovery is complex and can be unpredictable, it is unclear whether nerve recovery was attributable to the drug of choice, mechanism of injury (idiopathic vs iatrogenic), or natural recovery. Additionally, it is also unclear whether medications that help preserve facial function be able to restore facial nerve function. A majority of the articles in the meta‐analysis was considered to have a moderate or severe risk of bias. More randomized controlled trials are needed to distinguish this difference. However, given the functional and quality of life impact of facial paralysis, the ethical balance between the treatment and control groups is important to consider.

Conclusion

Nimodipine significantly improved HB score with a mean difference of 1.66 but was not significant in demonstrating successful recovery (HB score ≤3) when compared to controls. Given the heterogeneity in the studies on nimodipine, more studies are needed to elucidate the effects of nimodipine on facial nerve recovery before any clinical guidance can be provided. Pentoxifylline showed a significant difference in full recovery (HB score 1) when compared to controls; however, it is difficult to make conclusions based on one study. Coenzyme Q10 did exhibit a clinical difference in HB score improvement when compared to controls. ExoFlo™ (extracellular vesicles) may have a benefit in improving facial nerve recovery; however, more studies with larger sample sizes are needed. While many other beneficial drugs found in the literature are associated with facial nerve recovery, there is a lack of data in human studies. Further research is warranted to collect more data on currently available medications and uncover additional medications that promote facial nerve recovery.

Author Contributions

Kimberly Chan, conceptualization, data curation, investigation, methodology, visualization, writing—original draft, writing—review and editing; Cheng Ma, data curation, formal analysis, investigation, visualization, writing—review and editing; Bao Sciscent, data curation, investigation, writing—review and editing; Andreacarola Urso, data curation, investigation, writing—review and editing; Neerav Goyal, conceptualization, supervision, writing—review and editing; Jessyka Lighthall, conceptualization, supervision, writing—review and editing. All authors have reviewed and approved of the manuscript prior to submission.

Disclosures

Competing interests

None.

Funding source

None.